The purpose of this proposal is to elucidate the mechanism through which the reaction of antigen with cell-bound IgE antibody leads to the release of chemical mediators from mast cells. Research plan is based on our recent findings which indicated that bridging of IgE-receptors by divalent anti-receptor antibody induced non-cytotoxic histamine release, while bridging of some other membrane components do not necessarily induce the reaction. As anaphylactic reactions can be induced by IgG type homocytotropic antibodies, we shall study 1) possible relationship between IgE-receptor and Fc gamma receptors on the same mast cells, and 2) whether the antibodies specific for the Fc gamma receptors may trigger histamine release. In view of an important role of IgE-receptor in triggering of mediator release, we shall analyze membrane events in which IgE receptors are involved. Thus, 3) attempts will be made to identify membrane-associated enzyme(s) which is activated by bridging of IgE receptors. 4) Possible association between IgE receptors and cytoskeletal elements, such as actin and myosin, will be investigated. Since IgE receptors were found not only on mast cells but also on a sup-population of lymphocytes, 5) we shall study similarities and/or difference between IgE receptors and mast cells and those on lymphocytes. In addition, 6) research is planned to study possible role of IgE-receptor-bearing lymphocytes in IgE biosynthesis.